In many pathological conditions there is an imbalance of the partition of fluid and solutes between the vascular and extravascular space. Fluid and solute exchange across the microvasculature is partially controlled by the interstitial hydrostatic and oncotic pressures. Changes in the hydration of the interstitial gel matrix, which is composed of glycosaminoglycans and collagen, may affect the interstitial oncotic pressure by altering the distribution of extravascular plasma proteins. We propose to study the effects of edema on the transport and distribution of plasma proteins in the interstitial space and lymph from tissues in the hindpaws of rabbits. A comparison will be made between these measurements in skin and skeletal muscle to test if differences in the composition of the interstitial matrix between these tissues may cause differences in the interstitial transport and distribution of plasma proteins. Edema will be produced both by venous congestion and increased microvascular protein permeability in order to test the hypothesis that the protein concentration of edema fluid alters the gel-matrix hydration. Measurements of the extravascular distribution volumes of radiolabelled plasma proteins and sucrose will provide estimates of the degree of interstitial exclusion of proteins. Alterations in the fluid-gel matrix will be studied by comparing the initial rate of plasma-to-lymph equilibration for a small protein equilibration in the interstitial space with that in lymph. The results of these studies will provide information on the role of the interstitial matrix in tissue fluid balance and on the etiology of edema formation.